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Biomedical subjects

K Mizutani

Publications and source records attributed to K Mizutani.

At least 19 recordsLinked to original sources
PubMed2006

Anisotropy and corotation of galactic cosmic rays.

The intensity of Galactic cosmic rays is nearly isotropic because of the influence of magnetic fields in the Milky Way. Here, we present two-dimensional high-precision anisotropy measurement for energies from a few to several hundred teraelectronvolts (TeV), using the large data sample of the Tibet Air Shower Arrays. Besides revealing finer details of the known anisotropies, a new component of Galactic cosmic ray anisotropy in sidereal time is uncovered around the Cygnus region direction. For cosmic-ray energies up to a few hundred TeV, all components of anisotropies fade away, showing a corotation of Galactic cosmic rays with the local Galactic magnetic environment. These results have broad implications for a comprehensive understanding of cosmic rays, supernovae, magnetic fields, and heliospheric and Galactic dynamic environments.

Journal Article↗
PubMed2006

Soluble HLA-G expression and renal graft acceptance.

HLA-G is a potentially interesting molecule associated with immunosuppressive function. We survey here the presence of soluble HLA-G (sHLA-G) in serial serum samples of renal transplants. A total of 330 sera of from 65 patients were tested for sHLA-G with ELISA. IgG/IgM antibodies to HLA, and MICA antibodies were also previously tested. After serial analysis of the 65 patients' 330 sera, 50% of 26 patients in functioning group had consistent sHLA-G expression or became positive, in comparison to 20.5% among 39 patients who rejected their transplants (p=0.013). Thus sHLA-G was associated with functioning transplants. Eighty percent (77 of 96) of the HLA IgG positive sera had no sHLA-G expression, while 81.4% (83 of 102) of the HLA-G(+) sera had no HLA IgG (p=0.005), which showed a negative association between sHLA-G and the presence of HLA IgG antibodies (which was previously been shown to be associated with failure). In this preliminary survey, sHLA-G was found in the serum of about 30% of renal transplant patients. sHLA-G had a negative association with allograft failure from chronic rejection, and a negative relationship with the production of HLA IgG antibodies. The significance of sHLA-G in renal transplants remains to be determined.

Adult↗
PubMed2006

Acoustical experiment of yogurt fermentation process.

One of the important factors through food manufacturing is hygienic management. Thus, food manufactures prove their hygienic activities by taking certifications like a Hazard Analysis and Critical Control Point (HACCP). This concept also applies to food monitoring. Acoustical measurements have advantage for other measurement in food monitoring because they make it possible to measure with noncontact and nondestructive. We tried to monitor lactic fermentation of yogurt by a probing sensor using a pair of acoustic transducers. Temperature of the solution changes by the reaction heat of fermentation. Consequently the sound velocity propagated through the solution also changes depending on the temperature. At the same time, the solution change its phase from liquid to gel. The transducers usage in the solution indicates the change of the temperature as the change of the phase difference between two transducers. The acoustic method has advantages of nondestructive measurement that reduces contamination of food product by measuring instrument. The sensor was inserted into milk with lactic acid bacterial stain of 19 degrees C and monitored phase retardation of propagated acoustic wave and its temperature with thermocouples in the mild. The monitoring result of fermentation from milk to Caspian Sea yogurt by the acoustic transducers with the frequency of 3.7 MHz started to show gradient change in temperature caused by reaction heat of fermentation but stop the gradient change at the end although the temperature still change. The gradient change stopped its change because of phase change from liquid to gel. The present method will be able to measure indirectly by setting transducers outside of the measuring object. This noncontact sensing method will have great advantage of reduces risk of food contamination from measuring instrument because the measurement probes are set out of fermentation reactor or food containers. Our proposed method will contribute to the hygienization for the food manufacture industry.

Acoustics↗
PubMed2006

Expression of clusterin, XIAP and survivin, and their changes by camptothecin (CPT) treatment in CPT-resistant PC-3 and CPT-sensitive LNCaP cells.

AIM: Clusterin and IAPs (inhibitor of apoptosis proteins), such as survivin and XIAP, are known to be related to chemo-resistance in several cancer cells. In the current study, we investigated their expression levels in human prostate cancer cell lines, LNCaP and PC-3 which are sensitive and resistant to camptothecin (CPT), topoisomerase I inhibitor, respectively. METHODS: LNCaP and PC-3 cells were cultured in the presence of CPT, cell death was evaluated using Hoechst 33342 and propidium iodide (PI) double staining. The expression of clusterin, XIAP and survivin on mRNA and protein levels was investigated by semi-quantitative RT-PCR and Western blotting, respectively. RESULTS: Our data showed that 24 h treatment of LNCaP cells with 0.5 and 3.0 microM CPT resulted in higher number of apoptotic cells, than that in PC-3 cells. Western blot analysis revealed that the clusterin level in PC-3 cells was 5-fold higher than that in LNCaP cells. In contrast, XIAP expression level in PC-3 cells was lower than that in LNCaP cells, and survivin levels were similar in these two cell lines. Treatment with 0.5 and 3.0 microM CPT resulted in the reduced survivin and XIAP expression in both cell lines, while clusterin expression remained unchanged in LNCaP cells, but was increased in PC-3 cells. CONCLUSION: The results suggest that clusterin may take a greater part in CPT-resistance than survivin and XIAP in PC-3 cells.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Decreased expression of haemoglobin beta (HBB) gene in anaplastic thyroid cancer and recovery of its expression inhibits cell growth.

Anaplastic thyroid cancer (ATC) is one of the most fulminant and foetal diseases in human malignancies. However, the genetic alterations and carcinogenic mechanisms of ATC are still unclear. Recently, we investigated the gene expression profile of 11 anaplastic thyroid cancer cell lines (ACL) and significant decreased expression of haemoglobin beta (HBB) gene in ACL. Haemoglobin beta is located at 11p15.5, where loss of heterozygosity (LOH) was reported in various kinds of cancers, including ATC, and it has been suggested that novel tumour suppressor genes might exist in this region. In order to clarify the meaning of decreased expression of HBB in ATC, the expression status of HBB was investigated with ACL, ATC, papillary thyroid cancer (PTC) and normal human tissues. Haemoglobin beta showed significant decreased expression in ACLs and ATCs; however, in PTC, HBB expressed equal to the normal thyroid gland. In addition, HBB expressed in normal human tissues ubiquitously. To validate the tumour-suppressor function of HBB, cell growth assay was performed. Forced expression of HBB in KTA2 cell, which is a kind of ACL, significantly suppressed KTA2 growth. The mechanism of downregulation of HBB in ATC is still unclear; however, our results suggested the possibility of HBB as a novel tumour-suppressor gene.

Carcinoma↗
PubMed2005

CD16+CD57- natural killer cells in multifocal motor neuropathy.

We analyzed the CD16+CD57- lymphocyte subset, which is considered to have strong natural killer (NK) cell activity, in peripheral blood from patients with chronic immune-mediated neuropathies and patients with other neurological diseases. We found that the ratio of CD16+CD57- NK cells to total lymphocytes was increased in 4 of 6 patients with multifocal motor neuropathy (MMN) with persistent conduction block. Since the CD16 molecule is an Fc receptor for immunoglobulin G (IgG), high-dose intravenous immunoglobulin (IVIg) may interfere with CD16+CD57- NK cells via Fc receptor blockade. In addition, cyclophosphamide (Cy) is often used to suppress NK cells. Therefore, our findings may partly account for the effectiveness of IVIg or Cy, which is the current treatment of choice for MMN.

Adult↗
PubMed2004

Observation by an air-shower array in Tibet of the multi-TeV cosmic-ray anisotropy due to terrestrial orbital motion around the Sun.

We report on the solar diurnal variation of the galactic cosmic-ray intensity observed by the Tibet III air shower array during the period from 1999 to 2003. In the higher-energy event samples (12 and 6.2 TeV), the variations are fairly consistent with the Compton-Getting anisotropy due to the terrestrial orbital motion around the Sun, while the variation in the lower-energy event sample (4.0 TeV) is inconsistent with this anisotropy. This suggests an additional anisotropy superposed at the multi-TeV energies, e.g., the solar modulation effect. This is the highest-precision measurement of the Compton-Getting anisotropy ever made.

Journal Article↗
PubMed2004

Comprehensive gene expression profiling of anaplastic thyroid cancers with cDNA microarray of 25 344 genes.

Little is known about the genetic mechanisms of anaplastic thyroid cancer (ATC). This is the most virulent of all human malignancies, and it is believed to result from transformation of differentiated thyroid cancers. To identify a set of genes involved in the development of ATC, we investigated expression profiles of 11 cell lines derived from ATC using a cDNA microarray representing 25 344 genes. Semi-quantitative RT-PCR experiments carried out for some genes that had shown altered expression on the microarray verified frequent over-expression of destrin, HSPA8, stathmin, LDH-A, ATP5A1, PSMB6, B23, HDP-1 and LDH-B, and frequent under-expression of thyroglobulin, PBP and c-FES/FPS genes among the cell lines and also among ten primary ATCs. In addition to mRNA expression studies, up-regulation of GDI2, destrin and stathmin were confirmed with immunohistochemical analysis. The extensive list of genes identified provides valuable information towards understanding the development of ATC, and provides a source of possible biomarkers for diagnosis and/or molecular targets for the development of novel drugs to treat ATC.

Biomarkers, Tumor↗
PubMed2003

Identification of two types of synaptic activity in the earthworm nervous system during locomotion.

In the ventral nervous system of the earthworm, a central pattern generator and motor neurons are activated during locomotion. We have previously reported that bath application of octopamine (OA) induces fictive locomotion in the earthworm, and the burst frequency of electrical activity from the first lateral nerves increases with OA concentration. However, there are no reports concerning locomotor neural networks in the earthworm. To identify neural networks involved in fictive locomotion, we optically monitored activity-dependent fluorescent staining in the earthworm ventral nerve cord (VNC) with a styryl dye, N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl)pyridinium dibromide (FM1-43), and a confocal laser scanning microscope. OA induces FM1-43 fluorescence in a dose-dependent manner, with bright fluorescent spots of 3-10 microm in diameter observed to be localized around specified neurons in the segmental ganglion of the VNC. We compared OA dose-response curves for FM1-43 fluorescence with the bursting frequency for fictive locomotion, and found that two types of curves could be identified: one fluorescence response shows a similar dose-dependency to that of the burst frequency, while another response has a higher sensitivity to OA. From these results, we suggest that OA acts as one of the neuromodulators for the earthworm locomotion. This is the first attempt to record motor and inter-neuronal activities simultaneously in a locomotor network in the earthworm.

Action Potentials↗
PubMed2001

Use of marginal organs from non-heart-beating cadaveric kidney donors.

BACKGROUND: The severe shortage of cadaver donor kidneys for transplantation has prompted many centers to utilize older donor kidneys, which have been associated with lower graft survival rates. The aim of the present study was to examine the availability and feasibility of considering kidneys from donors over the age of 60. METHOD: We studied 252 cadaveric renal transplant recipients (156 males, 96 females) who received kidneys from uncontrolled non-heart-beating donors between 1987 and 1997. We performed in situ cooling with especially designed double-balloon catheters to minimize warm ischemic kidney damage. Recipients were classified according to donor age ( age 60), and we examined graft survival rates. All patients were followed for a minimum of 1 year after transplantation. RESULTS: Graft survival rates for recipients of kidneys from the older donor group at 1, 5, and 10 years after transplantation were 77%, 37%, and 30%, respectively. Corresponding values for the younger donor kidney recipients were 87%, 64%, and 47%, respectively (P=0.0011). Improved survival rates were noted when older kidneys were used for lighter weight recipients (<54 kg). No other significant factors impacted on older donor graft survival rates. CONCLUSION: Older donor kidneys are associated with poorer graft survival rates. However, kidney transplants from older donors can be quite effective in lighter weight recipients (<54 kg).

Adult↗
PubMed2001

Involvement of phosphorylation of myosin phosphatase by ROCK in trabecular meshwork and ciliary muscle contraction.

The control of smooth muscle contraction is an important factor in maintaining normal intraocular pressure. However, the specific factors causing changes in control by phosphorylation/dephosphorylation schemes in the eye are not well-defined. The purposes of this experiment were to (i) determine the localization of ROCK (Rho-associated, coiled coil-forming kinase) in monkey and rabbit eye tissues and (ii) measure phosphorylation of ROCK substrate during trabecular meshwork or ciliary muscle contraction induced by carbachol. We found that mRNAs for both ROCK I and II were expressed in most eye tissues from rabbit and monkey. Proteins for ROCK I and II were present in all eye tissues studied except lens. When trabecular meshwork or ciliary muscle were incubated with carbachol to induce contraction, phosphorylation of the myosin-binding subunit (MBS) of myosin phosphatase, a substrate for ROCK, started within 1 min and continued for at least 1 h. This phosphorylation was well correlated with contraction of trabecular meshwork or ciliary muscle. These results suggested that ROCK might regulate contraction of trabecular meshwork or ciliary muscle through phosphorylation of MBS of myosin phosphatase.

Animals↗
PubMed2001

Anion-mediated Fe3+ release mechanism in ovotransferrin C-lobe: a structurally identified SO4(2-) binding site and its implications for the kinetic pathway.

The differential properties of anion-mediated Fe(3+) release between the N- and C-lobes of transferrins have been a focus in transferrin biochemistry. The structural and kinetic characteristics for isolated lobe have, however, been documented with the N-lobe only. Here we demonstrate for the first time the quantitative Fe(3+) release kinetics and the anion-binding structure for the isolated C-lobe of ovotransferrin. In the presence of pyrophosphate, sulfate, and nitrilotriacetate anions, the C-lobe released Fe(3+) with a decelerated rate in a single exponential progress curve, and the observed first order rate constants displayed a hyperbolic profile as a function of the anion concentration. The profile was consistent with a newly derived single-pathway Fe(3+) release model in which the holo form is converted depending on the anion concentration into a "mixed ligand" intermediate that releases Fe(3+). The apo C-lobe was crystallized in ammonium sulfate solution, and the structure determined at 2.3 A resolution demonstrated the existence of a single bound SO(4)(2-) in the interdomain cleft, which interacts directly with Thr(461)-OG1, Tyr(431)-OH, and His(592)-NE2 and indirectly with Tyr(524)-OH. The latter three groups are Fe(3+)-coordinating ligands, strongly suggesting the facilitated Fe(3+) release upon the anion occupation at this site. The SO(4)(2-) binding structure supported the single-pathway kinetic model.

Anions↗
PubMed2001

Sensorimotor demyelinating neuropathy with IgM antibody against gangliosides GD1a, GT1b and GM3.

We report a patient with sensorimotor demyelinating neuropathy with high-titer IgM antibody against gangliosides GD1a, GT1b and GM3. The patient was a 65-year-old male who was hospitalized with chief complaints of muscular weakness of all limbs and numbness of the hands and feet. Nerve-conduction studies revealed reduced conduction velocities of the motor nerves with increased temporal dispersion and loss of sensory nerve action potentials. Treatment with steroids was ineffective. IgM antibody against GD1a, GT1b and GM3, which are known to be the ligands for myelin-associated glycoprotein (MAG), might have played a role in the demyelination in this patient by inhibiting adhesion between myelin and axonal membrane.

Aged↗
PubMed2001

Domain closure mechanism in transferrins: new viewpoints about the hinge structure and motion as deduced from high resolution crystal structures of ovotransferrin N-lobe.

The crystal structure of holo hen ovotransferrin N-lobe refined at 1.65 A resolution has been obtained. The final model gave an R-factor of 0.173 in the resolution range between 10.0 and 1.65 A. The comparison of the structure with previous high-resolution apo and Fe(3+)-loaded, domain-opened intermediate structures provides new viewpoints on the domain closure mechanism upon Fe(3+) uptake in ovotransferrin N-lobe. Overall, conformational transition follows the common mechanism that has been first demonstrated for lactoferrin N-lobe; the domains 1 and 2 rotate 49.7 degrees as rigid bodies with a translation of 2.1 A around a screw-axis that passes through the two interdomain beta-strands (89-94 and 244-249). It is generally believed that the two strands display a hinge-like motion. Here, the latter strand indeed displays an ideal hinge nature: the segments 244-246 and 248-249 behave as a part of the rigid body of domain 2 and that of domain 1, respectively, and a sharp bend upon the domain closure is largely accounted for by the changes in the torsion angles phi and psi of Val247. We find, however, that the mode of the conformational change in the first beta-strand is much more complex. Two of the five inter beta-strand hydrogen bonds undergo crucial exchanges: from Ser91-N...Val247-O and Thr89-O...Ala249-N in the open apo and intermediate structures into Tyr92-N...Val247-O and Thr90-O...Ala249-N in the closed holo structure. These exchanges, which may be triggered in the intermediate state by modulation in the topological relation between the Fe(3+)-ligated hinge residue Tyr92-OH and the anion anchor residues of helix 5, are accompanied by a large conformational change and extensive hydrogen bonding rearrangements in a long stretch of segment of Glu82 to Tyr92. Such structural transition would work as a driving force for the domain closure, which highlights a "door closer"-like role, in addition to the canonical-hinge role, for the interdomain polypeptide segment pair. As an alternative hinge that secures the correct domain motion by being placed on a significant distance from the beta-strand hinge, we point out the participation of the van der Waals contacts formed between domain 1 residue of Met331 and domain 2 residues of Trp125, Ile129 and Trp140.

Animals↗